Bacteriostatic cells instead of bacteriostatic antibiotics?

Abstract

This year we commemorate the centennial of the birth of the mature concept of bacteriostasis by John W. Churchman at Cornell University Medical School. The term bacteriostasis has primarily been applied to antibiotics (bacteriostatic antibiotics). In this Opinion paper, we are revisiting this concept by suggesting that bacteriostasis essentially reflects a distinct cellular status (or "cell variant") characterized by the inability to be killed as a consequence of an antibiotic-induced stress impacting on bacterial physiology/metabolism (growth). Note that the term "bacteriostasis" should not be associated only with antimicrobials but with many stressful conditions. In that respect, the drug promotion of bacteriostasis might resemble other types of stress-induced cellular differentiation, such as sporulation, in which spores can be considered "bacteriostatic cells" or perhaps as persister bacteria, which can become "normal cells" again when the stressful conditions have abated.IMPORTANCEThis year we commemorate the centennial of the birth of the mature concept of bacteriostasis by John W. Churchman at Cornell University Medical School. The term bacteriostasis has primarily been applied to antibiotics (bacteriostatic antibiotics). In this Opinion paper, we are revisiting this concept by suggesting that some antibiotics are drugs that induce bacteria to become bacteriostatic. Cells that are unable to multiply, thereby preventing the antibiotic from exerting major lethal effects on them, are a variant ("different") type of cells, bacteriostatic cells. Note that the term "bacteriostasis" should not be associated only with antimicrobials but with many stressful conditions. In that respect, the drug promotion of bacteriostasis might resemble other types of stress-induced cellular differentiation, such as sporulation, in which spores can be considered "bacteriostatic cells" or perhaps as persister bacteria, which can become "normal cells" again when the stressful conditions have abated.

Keywords: antibiotic mode of action; bacteriostatic antibiotics; bacteriostatic cells.

Fig 1

Antibiotics produce cellular bacteriostasis. (a) Schema of a bacterial cell with antibiotic targets: outer membrane (brown), cell wall (black), cytoplasmic membrane (green), ribosomes (blue), nucleoid (red, twisted), and metabolism (sequential blue squares). (b) The antibiotic exposure (thick red arrow) influences the function of their target(s) (thin red arrows). (c) The modification of target functioning influences other functions in the cell’s physiological interactive network (blue broken lines), producing a functionally altered cell. (d) Gray prohibitory signs represent the antibiotic’s inability to produce a lethal effect; the cells have been converted into bacteriostatic cells. If the antibiotic exposure is discontinued, the cell returns to its susceptible status (a).